Loss of Leptin Actions in Obesity: Two Concepts with Cardiovascular Implications
Abstract
Obesity is associated with increased risk of hypertension and heart disease. Leptin has recently been linked to increased risk of cardiovascular disease. We review briefly here two concepts regarding loss of leptin actions that have potential implications for cardiovascular disease. These are: 1. the concept of selective leptin resistance; and 2. the concept that loss of leptin action results in lipid accumulation and lipotoxicity of skeletal muscle, pancreatic islet cells, and heart and, thereby, promotes insulin resistance, insulin deficiency and cardiac dysfunction, respectively.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Selective leptin resistance occurs in obesity.
“An intriguing aspect to consider with respect to the influence of leptin on the myocardium is the concept that selective leptin resistance occurs in obesity (60, 61, 222, 223).”
From Cardiac remodeling in obesity (2008) · cites this paper as [222]
Initial studies suggested that while the effects of leptin on satiety and energy metabolism were resistant, the sympathoexcitatory effects were maintained.
“Initial studies purporting this concept suggested that while the effects of leptin on satiety and energy metabolism were resistant, the sympathoexcitatory effects were maintained (60, 61, 222, 223, 290, 291).”
From Cardiac remodeling in obesity (2008) · cites this paper as [222]
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419 · see citing works
Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans
Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., Bauer, T. L., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602013340503 · Cited by 6,326 · see citing works
Identification and expression cloning of a leptin receptor, OB-R.
Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G. J., Campfield, L. A., Clark, F. T., Deeds, J., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90151-5 · Cited by 3,496 · see citing works
Congenital leptin deficiency is associated with severe early-onset obesity in humans
Montague, C. T., Farooqi, I. S., Whitehead, J. P., Soos, M. A., Rau, H., Wareham, N. J., Sewter, C. P., Digby, J. E., Mohammed, S. N., Hurst, J. A., et al. (1997) · Nature · doi:10.1038/43185 · Cited by 2,936 · see citing works
A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction
Clément, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., Gourmelen, M., Dina, C., Chambaz, J., Lacorte, J.-M., et al. (1998) · Nature · doi:10.1038/32911 · Cited by 2,346 · see citing works
Lipotoxic heart disease in obese rats: Implications for human obesity
Zhou, Y.-T., Grayburn, P., Karim, A., Shimabukuro, M., Higa, M., Baetens, D., Orci, L., & Unger, R. H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.4.1784 · Cited by 1,265 · see citing works
Leptin-Replacement Therapy for Lipodystrophy
Oral, E. A., Simha, V., Ruiz, E., Andewelt, A., Premkumar, A., Snell, P., Wagner, A. J., DePaoli, A. M., Reitman, M. L., Taylor, S. I., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa012437 · Cited by 1,247 · cited 1× · see citing works
“Administration of leptin to these patients decreases intramyocellular lipids and produces a prompt and sustained improvement in insulin sensitivity and glucose intolerance (23,24).”
BackgroundLeptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy
Shimomura, I., Hammer, R. E., Ikemoto, S., Brown, M. S., & Goldstein, J. L. (1999) · Nature · doi:10.1038/43448 · Cited by 1,038 · see citing works
Physiological response to long-term peripheral and central leptin infusion in lean and obese mice.
Halaas, J. L., Boozer, C., Blair-West, J., Fidahusein, N., Denton, D. A., & Friedman, J. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.16.8878 · Cited by 1,033 · see citing works
Receptor-mediated regional sympathetic nerve activation by leptin.
Haynes, W. G., Morgan, D. A., Walsh, S. A., Mark, A. L., & Sivitz, W. I. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119532 · Cited by 979 · see citing works
Self-citationWallace, A. M., McMahon, A. D., Packard, C. J., Kelly, A., Shepherd, J., Gaw, A., & Sattar, N. A. (2001) · Circulation · doi:10.1161/hc5001.101061 · Cited by 821 · see citing works
Chronic Leptin Infusion Increases Arterial Pressure
Shek, E. W., Brands, M. W., & Hall, J. E. (1998) · Hypertension · doi:10.1161/01.hyp.31.1.409 · Cited by 686 · see citing works
Pathophysiological role of leptin in obesity-related hypertension
Aizawa-Abe, M., Ogawa, Y., Masuzaki, H., Ebihara, K., Satoh, N., Iwai, H., Matsuoka, N., Hayashi, T., Hosoda, K., Inoue, G., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8341 · Cited by 477 · see citing works
Diseases of liporegulation: new perspective on obesity and related disorders
Unger, R. H., & Orci, L. (2001) · The FASEB Journal · doi:10.1096/fj.00-0590 · Cited by 429 · see citing works
Leptin induces direct vasodilation through distinct endothelial mechanisms.
Lembo, G., Vecchione, C., Fratta, L., Marino, G., Trimarco, V., d’Amati, G., & Trimarco, B. (2000) · Diabetes · doi:10.2337/diabetes.49.2.293 · Cited by 329 · see citing works
Mark, A. L., Shaffer, R. A., Correia, M. L. G., Morgan, D. A., Sigmund, C. D., & Haynes, W. G. (1999) · Journal of Hypertension · doi:10.1097/00004872-199917121-00026 · Cited by 254 · see citing works
Self-citationThe Concept of Selective Leptin Resistance
Correia, M. L. G., Haynes, W. G., Rahmouni, K., Morgan, D. A., Sivitz, W. I., & Mark, A. L. (2002) · Diabetes · doi:10.2337/diabetes.51.2.439 · Cited by 218 · see citing works
Self-citationSelective leptin resistance: a new concept in leptin physiology with cardiovascular implications
Mark, A. L., Correia, M. L. G., Rahmouni, K., & Haynes, W. G. (2002) · Journal of Hypertension · doi:10.1097/00004872-200207000-00001 · Cited by 215 · see citing works
Self-citationSteinberg, G. R., Parolin, M. L., Heigenhauser, G. J. F., & Dyck, D. J. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00542.2001 · Cited by 207 · see citing works
Lipotoxic diseases of nonadipose tissues in obesity
Rh, U., & Orci, L. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801498 · Cited by 204 · see citing works
Simha, V., Szczepaniak, L. S., Wagner, A. J., DePaoli, A. M., & Garg, A. (2003) · Diabetes Care · doi:10.2337/diacare.26.1.30 · Cited by 123 · see citing works
Leptin physiology: a second look
Unger, R. H. (2000) · Regulatory Peptides · doi:10.1016/s0167-0115(00)00154-3 · Cited by 67 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Abel, E. D., Litwin, S. E., & Sweeney, G. (2008) · Physiological Reviews · doi:10.1152/physrev.00017.2007 · Cited by 736 · see citing works
MADANI, S., DEGIROLAMO, S., MUNOZ, D., LI, R., & SWEENEY, G. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2005.11.022 · Cited by 122 · see citing works
- Authors
- Mark, A. L., Correia, M. L. G., Rahmouni, K., & Haynes, W. G.
- Affiliations
- University of Iowa (US)
- Venue
- Clinical and Experimental Hypertension
- Publisher
- Informa UK Limited
- Published
- 2004-01
- Volume
- 26
- Issue
- 7-8
- Pages
- 629-636
- ISSN
- 0148-3927 (ISSN-L)
- 1064-1963
- 1525-6006
- OpenAlex
- W2028568978
- Cited by
- 32
- References
- 22
- Citations by year
- 2026: 1 · 2021: 1 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2014: 3 · 2013: 1 · 2012: 1
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical and Experimental Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- American Heart Association
- National Institutes of Health (5p50hl044546-05)
- National Heart, Lung, and Blood Institute (HL-14388, HL-44546, P01HL014388)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- leptin, obesity, leptin resistance, cardiovascular disease, hypertension, lipotoxicity, lipid accumulation, skeletal muscle, pancreatic islet cells, cardiac dysfunction, insulin resistance, insulin deficiency
- MeSH terms
- Animals, Heart Diseases, Humans, Hypertension, Obesity, Risk Factors, Leptin, Lipid Metabolism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
